Proposed abstract for: MacPherson, D., J. Sage, T. Kim, D. Ho, M. E. McLaughlin, and T. Jacks. Cell Type-specific Effects of Rb
Deletion in the Murine Retina. Genes Dev. 18, no. 14 (Jul 15, 2004): 1681-94. Epub 2004 Jul 01. PMID: 15231717 [PubMed indexed for MEDLINE]. Courtesy of Sharon Lawrence. Used with permission.
Courtesy of Sharon Lawrence. Used with permission.
Sharon Lawrence
7.342 - Cancer Biology
Project 1
Due Date: October 19, 2004
The tumor-suppressing Rb gene regulates cell processes, such as Sphase entry, apoptosis and terminal differentiation. When found in humans, a
mutation in this gene greatly increases the chance of developing retinoblastoma.
Therefore, it is our belief that determining the role of Rb in retinal development
will lead to a better understanding of the cause of retinoblastoma.
We studied NesCre1 transgenic mice with Rb mutation alone, and also
with compound mutations involving Rb and p53, p107, or p130, in order to
determine the effects of these mutations on retinal development. We found that
Rb deficiency disrupts exit from the cell-cycle, which leads to p53-independent
apoptosis in many retinal cells, such as photoreceptors, bipolar cells, and retinal
ganglion cells, and abnormalities and nuclear disorganization in amacrine cells
and other types of cells. Mutations in both the Rb and p107 genes together led
to massive retinal dysplasia and high levels of apoptosis. Mutants lacking both
Rb and p130, however, did not exhibit high levels of dysplasia, and apoptosis
levels were similar to levels observed in Rb mutants. These results helped to
further our understanding of the roles of the Rb gene and Rb family members in
the development of both specific retinal cells and, consequently, retinoblastoma.